The 2,11-cyclized cembranoids are a class of diterpenoids isolated from a variety of marine sources that display a range of biological activities.(1) Some 2,11-cyclized cembranoids reported to possess cytotoxic activity are shown below:

Sclerophytin A has been reported to exhibit growth inhibitory activity against the L1210 cell line with an IC50 of 1.0 ng/mL (3 nM).(2-4) Eleutherobin(5,6) and sarcodictyins(7,8) A and B are reported to exhibit taxol-like anti-mitotic activity.(9,10) There have been several reports of structure/activity relationship studies of sarcodictyin (11,12) or eleutherobin(13-16) analogs. However, there are fewer biological studies of any analogs of the more common isobenzofuran-containing 2,11-cyclized cembranoids.(17,18)
Recently, synthetic approaches have been developed for making selected cyclized cembranoids in which the isobenzofuran bicycle is assembled in as few as three steps from commercially available (S)-(+)-carvone using a highly stereoselective aldol-cycloaldol sequence.(19) This approach is used herein to prepare structurally related isobenzofurans that are nominal analogs of sclerophytin A.